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Summary: Mitochondrial function relies on the coordinated transcription of mitochondrial and nuclear genomes to assemble respiratory chain complexes. Across species, the SIN3 coregulator influences mitochondrial functions, but how its loss impacts mitochondrial homeostasis and metabolism in the context of a whole organism is unknown. Exploring this link is important because SIN3 haploinsufficiency causes intellectual disability/autism syndromes and SIN3 plays a role in tumor biology. Here we show that loss of C. elegans SIN-3 results in transcriptional deregulation of mitochondrial- and nuclear-encoded mitochondrial genes, potentially leading to mito-nuclear imbalance. Consistent with impaired mitochondrial function, sin-3 mutants show extensive mitochondrial fragmentation by transmission electron microscopy (TEM) and in vivo imaging, and altered oxygen consumption. Metabolomic analysis of sin-3 mutant animals revealed a mitochondria stress signature and deregulation of methionine flux, resulting in decreased S-adenosyl methionine (SAM) and increased polyamine levels. Our results identify SIN3 as a key regulator of mitochondrial dynamics and metabolic flux, with important implications for human pathologies.

ABSTRACTQuickly understanding the genomic changes that lead to pathogen emergence is necessary to launch mitigation efforts and reduce harm. In this study, we tracked in real time a 2022 bacterial plant disease outbreak in U.S. geraniums (Pelargonium × hortorum) caused by Xhp2022, a novel lineage of Xanthomonas hortorum. Genomes from 31 Xhp2022 isolates from seven states showed limited chromosomal variation and all contained a single plasmid (p93). Time tree and single nucleotide polymorphism whole-genome analysis estimated that Xhp2022 emerged within the last decade. The phylogenomic analysis determined that p93 resulted from the cointegration of three plasmids (p31, p45, and p66) found sporadically across isolates from previous outbreaks. Although p93 had a 49 kb nucleotide reduction, it retained putative fitness genes, which became predominant in the 2022 outbreak. Overall, we demonstrated, through rapid whole-genome sequencing and analysis, a recent, traceable event of genome reduction for niche adaptation typically observed over millennia in obligate and fastidious pathogens.IMPORTANCEThe geranium industry, valued at $4 million annually, faces an ongoing Xanthomonas hortorum pv. pelargonii (Xhp) pathogen outbreak. To track and describe the outbreak, we compared the genome structure across historical and globally distributed isolates. Our research revealed Xhp population has not had chromosome rearrangements since 1974 and has three distinct plasmids. In 2012, we found all three plasmids in individual Xhp isolates. However, in 2022, the three plasmids co-integrated into one plasmid named p93. p93 retained putative fitness genes but lost extraneous genomic material. Our findings show that the 2022 strain group of the bacterial plant pathogen Xanthomonas hortorum underwent a plasmid reduction. We also observed several Xanthomonas species from different years, hosts, and continents have similar plasmids to p93, possibly due to shared agricultural settings. We noticed parallels between genome efficiency and reduction that we see across millennia with obligate parasites with increased niche specificity.

Objetivo: Analisar as publicações científicas relacionadas à atuação do Enfermeiro na prevenção das toxemias gravídicas.Método: Revisão integrativa da literatura. As buscas das evidências científicas foram realizadas nas bases de dados: Literatura Latino-Americana e do Caribe em Ciências da Saúde, Base de Dados de Enfermagem e Medical Literature Analysis and Retrieval System Online via Biblioteca Virtual da Saúde e Scientific Electronic Library Online, utilizando-se dos termos de busca: Assistência de Enfermagem, Cuidados de Enfermagem, Enfermagem, Pré-eclâmpsia e Eclâmpsia, com auxílio dos operadores booleanos “AND” e “OR”. Resultado: Após a seleção, leitura e filtragem, identificaram-se 10 estudos para análise, que foram agrupados por similaridade semântica e discutidos em categorias temáticas, sendo elas: Atuação do Enfermeiro na prevenção das toxemias gravídicas e Dificuldades encontradas na atuação do Enfermeiro na prevenção das toxemias gravídicas. Conclusão: É notável que com a realização de um acompanhamento pré-natal de qualidade durante toda a gestação é possível detectar de forma precoce as alterações nos sinais clínicos causadas pela toxemias gravídicas e iniciar um tratamento adequado.

RESUMO Objetivo Verificar a aplicabilidade do teste de percepção de fala com figuras em crianças com síndrome de Down. Método Estudo observacional, descritivo e prospectivo, realizado em dois centros fonoaudiológicos, aprovado pelos Comitês de Ética em Pesquisa sob número 82522217.5.0000.5440 e 79510317.8.0000.5257. Participaram 41 crianças com síndrome de Down, de ambos os sexos, com idade entre dois anos e dez anos e 11 meses, as quais foram divididas em três grupos: GI (dois a quatro anos e 11 meses); GII (cinco a sete anos e 11 meses) e GIII (oito a dez anos e 11 meses). Foram realizados os procedimentos de anamnese, meatoscopia, audiometria tonal liminar, teste de limiar de recepção de fala com figuras e imitanciometria. Para a análise estatística, Teste Exato de Fisher com nível de significância de 5%. Resultados Ao ser analisado o número de acertos e erros, em relação à idade cronológica, foi encontrada significância para sete palavras: gelo, faca, vaca, chave, rato, cão e sol. Foi analisado, posteriormente, o desempenho no teste de fala com figuras, dos participantes desse estudo e o desempenho dos participantes do estudo que elaborou e validou este teste. Foi observado que, quando se equiparou a porcentagem de acertos nos dois grupos, as palavras com maior ocorrência de acertos foram: mão, casa e sapo. Conclusão: O teste aplicado nesse estudo proporciona a interpretação do resultado de forma clara e objetiva e independe da produção verbal da criança.

The kinase PAR-4/LKB1 is a major regulator of intestinal homeostasis, which prevents polyposis in humans. Moreover, its ectopic activation is sufficient to induce polarization and formation of microvilli-like structures in intestinal cell lines. Here, we use Caenorhabditis elegans to examine the role of PAR-4 during intestinal development in vivo. We show that it is not required to establish enterocyte polarity and plays only a minor role in brush border formation. By contrast, par-4 mutants display severe deformations of the intestinal lumen as well as supernumerary intestinal cells, thereby revealing a previously unappreciated function of PAR-4 in preventing intestinal hyperplasia. The presence of supernumerary enterocytes in par-4 mutants is not due to excessive cell proliferation, but rather to the abnormal expression of the intestinal cell fate factors end-1 and elt-2 outside the E lineage. Notably, par-4 mutants also display reduced expression of end-1 and elt-2 inside the E lineage. Our work thereby unveils an essential and dual role of PAR-4, which both restricts intestinal specification to the E lineage and ensures its robust differentiation., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Variants in the UNC45A cochaperone have been recently associated with a syndrome combining diarrhea, cholestasis, deafness, and bone fragility. Yet the mechanism underlying intestinal failure in UNC45A deficiency remains unclear. Here, biallelic variants in UNC45A were identified by next-generation sequencing in 6 patients with congenital diarrhea. Corroborating in silico prediction, variants either abolished UNC45A expression or altered protein conformation. Myosin VB was identified by mass spectrometry as client of the UNC45A chaperone and was found misfolded in UNC45AKO Caco-2 cells. In keeping with impaired myosin VB function, UNC45AKO Caco-2 cells showed abnormal epithelial morphogenesis that was restored by full-length UNC45A, but not by mutant alleles. Patients and UNC45AKO 3D organoids displayed altered luminal development and microvillus inclusions, while 2D cultures revealed Rab11 and apical transporter mislocalization as well as sparse and disorganized microvilli. All those features resembled the subcellular abnormalities observed in duodenal biopsies from patients with microvillus inclusion disease. Finally, microvillus inclusions and shortened microvilli were evidenced in enterocytes from unc45a-deficient zebrafish. Taken together, our results provide evidence that UNC45A plays an essential role in epithelial morphogenesis through its cochaperone function of myosin VB and that UNC45A loss causes a variant of microvillus inclusion disease.

The intestinal brush border is made of an array of microvilli that increases the membrane surface area for nutrient processing, absorption and host defense. Studies on mammalian cultured epithelial cells have uncovered some of the molecular players and physical constraints required to establish this apical specialized membrane. However, the building and maintenance of a brush border in vivo has not yet been investigated in detail. Here, we combined super-resolution imaging, transmission electron microscopy and genome editing in the developing nematode Caenorhabditis elegans to build a high-resolution and dynamic localization map of known and new brush border markers. Notably, we show that microvilli components are dynamically enriched at the apical membrane during microvilli outgrowth and maturation, but become highly stable once microvilli are built. This new toolbox will be instrumental for understanding the molecular processes of microvilli growth and maintenance in vivo, as well as the effect of genetic perturbations, notably in the context of disorders affecting brush border integrity., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)